Abstract

The increasing incidence and unique biological features of lung cancer in women has prompted renewed interest in the role of sex hormones in this disease. We previously showed that progesterone (P4) inhibited lung cancer tumorigenesis and progression. Here, we investigated the effects of P4 on expression of long noncoding RNAs (lncRNAs) and target mRNAs in lung cancer cells. We performed high-throughput microarray and bioinformatics analysis to identify differentially expressed lncRNAs and mRNAs in the untreated and the P4-treated A549 human lung cancer cells. In total, 692 lncRNAs and 268 mRNAs were significantly differentially expressed in the P4-treated A549 cells compared to the untreated A549 cells (> 2-fold change, p < 0.05). Of the lncRNAs, 82 and 610 were up-regulated and down-regulated, respectively. Gene ontology, pathway and network analyses showed that many of the mRNAs were involved in the regulation of classical pathways, including Notch signaling. Differential expression of a lncRNA signature composed of NONHSAT000264, FR075921, FR324124, linc-TRIM58, RP1-93H18.7, RP11-120 K9.2, RP11-134F2.2 and NONHSAG024980 was validated by quantitatuve reverse transcriptase-polymerase chain reaction analysis. This is the first report of differentially expressed lncRNAs in the P4-treated lung cancer cells. The results suggest that lncRNAs could serve as potential therapeutic targets for P4-sensitive lung cancer.

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